Five years after the first season, unusual occurrences of genuine humans painfully transforming into flesh-eating monsters known as Amazonz have increased to dangerous levels. To that end, the Japanese feds have officially allowed bounty hunters to exterminate these monsters.

Chihiro/Kamen Rider Amazon Neo, an Amazonz boy who rejects his monstrous existence and yearns to be human and Iyu, formerly a human girl, resuscitated into a Amazonz, meet each other and want to be together in a world that wants them dead. Can they survive and truly become human?!